Pulmonary lymphangioleiomyomatosis (LAM), a disease of young women, is characterized by proliferation of abnormal smooth muscle cells (LAM cells), which often differ from normal pulmonary smooth muscle cells by frequently having estrogen (ER) and progesterone (PR) receptors. To evaluate the relationships among several factors related to proliferation and apoptosis in LAM cells, we employed immunohistochemical methods for the localization of Bcl-2 and MCL-1 (inhibitors of apoptosis), Bax (a promoter of apoptosis), c-Myc (an apoptosis-related oncoprotein), proliferating cell nuclear antigen (PCNA, an indicator of mitotic activity) and nick end labeling (to identify apoptotic cells) in lung tissues of 9 patients with LAM. In all patients, most LAM cells were Bax-positive. The LAM cells were positive for both Bcl-2 and ER in 5 patients, positive for only Bcl-2 in one patient, positive for only ER in another patient, and negative for both in 2 patients. Over 50% of the Bcl-2-positive LAM cells were also positive for ER. The reaction for c-Myc was positive in all patients. The immunoreactivity for Bcl-2 and MCL-1, which inhibit apoptosis, was more intense in LAM cells than in normal vascular and bronchial smooth muscle cells. In six patients, more than 50% of the LAM cells were PCNA-positive. Apoptosis was infrequent in LAM cells. Our results suggest that the expression of Bcl-2 in LAM cells may be related to hormonal regulation, and that, by decreasing apoptosis, Bcl-2 and related proteins contribute to the imbalance between proliferation and death of LAM cells.